Ion channels are transmembrane proteins that mediate transport of ions across cell membranes. These channels are pervasive throughout most cell types and important for regulating cellular excitability and homeostasis. Ion channels participate in numerous cellular processes such as action potentials, synaptic transmission, hormone secretion, and muscle contraction. Many important biological processes in living cells involve the translocation of cations, such as calcium (Ca2+), potassium (K+), and sodium (Na+) ions, through ion channels. Cation channels represent a large and diverse family of ion channels that are recognized as important drug targets.
Movement of physiologically relevant substrates through ion channels can be traced by a variety of physical, optical, or chemical techniques. Optical methods permit measurement of the entire course of ion flux in a single cell as well as in groups of cells. The advantages of monitoring transport by fluorescence techniques include the high level of sensitivity of these methods, temporal resolution, modest demand for biological material, lack of radioactivity, and the ability to continuously monitor ion transport to obtain kinetic information.
Thallium-sensitive, fluorescence-based assays are available for identifying modulators of ion channels, channel-linked receptors or ion transporters. For example, U.S. Patent Publication No. 20020168625, which is incorporated by reference herein, describes the use of thallium to measure ion channel activity for potassium, sodium, calcium, and other ions; and U.S. Patent Publication No. 20100279314, which is incorporated by reference herein, provides additional background on the use of thallium reagents and assays.
Despite available assays and indicators, there exists a need for improved compounds, compositions, and methods for screening agents that modulate cation channel activity. Moreover, there exists a need for improved high throughput screening methods to screen large libraries or groups of potential modulators.